Abstract
BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health. METHODS: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS-CoV by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues. RESULTS: MERS-CoV aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-CoV instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-CoV aerosol-infected mice than in the MERS-CoV instillation-inoculated mice. CONCLUSION: hDPP4 transgenic mice were successfully infected with MERS-CoV aerosols via an animal nose-only exposure device, and aerosol- and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.